Background <p>Radiolabeled [^195mPt]cisplatin has been developed as a tool to determine the biodistribution of cisplatin in vivo through SPECT imaging and possibly aid in patient-selection. This feasibility study aimed to evaluate the (radiation) safety, biodistribution, and image quality of [^195mPt]cisplatin SPECT/CT in patients with non-small cell lung cancer (NSCLC). [^195mPt]Cisplatin was produced under GMP standards. Six patients received 100 MBq [^195mPt]cisplatin in their second or third week of chemoradiation therapy. Planar and SPECT/CT imaging were acquired at 1.5, 48, 120 and 168&#xa0;h post-administration. Segmentation on SPECT for biodistribution and dosimetry was achieved using TotalSegmentator in 3DSlicer, and organ specific time-activity curves were generated through a mono-exponential curve fit. Effective and absorbed doses were obtained with S-values from IDAC-Dose 2.1. Toxicity was assessed using CTCAE criteria.</p> Results <p>Six NSCLC patients received 100.9 ± 3.3 MBq [^195mPt]cisplatin at a radioactivity concentration of 11.1 ± 4.9 MBq/mL. No adverse events above grade 2 were observed. [^195mPt]Cisplatin had a long retention time with an effective half-life of 74.8&#xa0;h. Uptake was highest in the liver and kidneys, which also resulted in the highest absorbed dose at 48.6 ± 7.9 mGy and 38.4 ± 7.3 mGy, respectively. Tumor uptake was similar to blood, with a ratio of 1.0 ± 0.05.</p> Conclusion <p>[^195mPt]Cisplatin is safe to use for imaging in patients with NSCLC when injecting 100 MBq, reaching a mean effective dose of 14.6 ± 1.5 mSv. The image quality of [^195mPt]cisplatin was suitable for SPECT imaging and quantification. Tumor uptake was similar to blood.</p> Trial registration <p>CCMO, NL74272.031.21. Registered 28 January 2022, <a href="https://www.onderzoekmetmensen.nl/nl/trial/55147">https://www.onderzoekmetmensen.nl/nl/trial/55147</a>.</p>